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Final Rule.
SUMMARY
This regulation establishes tolerances for residues of etoxazole in or on orange and orange oil. Sumitomo Chemical Latin America through Valent USA Corporation requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
TABLE OF CONTENTS
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DATES:
ADDRESSES:
FOR FURTHER INFORMATION CONTACT:
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this action apply to me?
B. How can I get electronic access to other related information?
C. How can I file an objection or hearing request?
II. Summary of Petitioned-for Tolerance
III. Aggregate Risk Assessment and Determination of Safety
A. Toxicological Profile
B. Toxicological Points of Departure/Levels of Concern
C. Exposure Assessment
D. Safety Factor for Infants and Children
E. Aggregate Risks and Determination of Safety
IV. Other Considerations
A. Analytical Enforcement Methodology
B. International Residue Limits
C. Revisions to Petitioned-For Tolerances
V. Conclusion
VI. Statutory and Executive Order Reviews
VII. Congressional Review Act
List of Subjects in 40 CFR Part 180
PART 180[AMENDED]
TABLES
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Table 1Summary of Toxicological Doses and Endpoints for Etoxazole for Use in Human Health Risk Assessment
DATES:
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This regulation is effective December 2, 2015. Objections and requests for hearings must be received on or before February 1, 2016, and must be filed in accordance with the instructions provided in 40 CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES:
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The docket for this action, identified by docket identification (ID) number EPA-HQ-OPP-2014-0681, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory Public Docket (OPP Docket) in the Environmental Protection Agency Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal holidays. The telephone number for the Public Reading Room is (202) 566-1744, and the telephone number for the OPP Docket is (703) 305-5805. Please review the visitor instructions and additional information about the docket available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT:
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Susan Lewis, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; main telephone number: (703) 305-7090; email address: RDFRNotices@epa.gov.
SUPPLEMENTARY INFORMATION:
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I. General Information
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A. Does this action apply to me?
You may be potentially affected by this action if you are an agricultural producer, food manufacturer, or pesticide manufacturer. The following list of North American Industrial Classification System (NAICS) codes is not intended to be exhaustive, but rather provides a guide to help readers determine whether this documentapplies to them. Potentially affected entities may include:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
B. How can I get electronic access to other related information?
You may access a frequently updated electronic version of EPA's tolerance regulations at 40 CFR part 180 through the Government Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl. To access the OCSPP test guidelines referenced in this document electronically, please go to http://www.epa.gov/ocspp and select Test Methods and Guidelines.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an objection to any aspect of this regulation and may also request a hearing on those objections. You must file your objection or request a hearing on this regulation in accordance with the instructions provided in 40 CFR part 178. To ensure proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-2014-0681 in the subject line on the first page of your submission. All objections and requests for a hearing must be in writing, and must be received by the Hearing Clerk on or before February 1, 2016. Addresses for mail and hand delivery of objections and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the Hearing Clerk as described in 40 CFR part 178, please submit a copy of the filing (excluding any Confidential Business Information (CBI)) for inclusion in the public docket. Information not marked confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA without prior notice. Submit the non-CBI copy of your objection or hearing request, identified by docket ID number EPA-HQ-OPP-2014-0681, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov. Follow the online instructions for submitting comments. Do not submit electronically any information you consider to be CBI or other information whose disclosure is restricted by statute.
Mail: OPP Docket, Environmental Protection Agency Docket Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 20460-0001.
Hand Delivery: To make special arrangements for hand delivery or delivery of boxed information, please follow the instructions at http://www.epa.gov/dockets/contacts.html.
Additional instructions on commenting or visiting the docket, along with more information about dockets generally, is available at http://www.epa.gov/dockets.
II. Summary of Petitioned-for Tolerance
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In the Federal Register of March 4, 2015 (80 FR 11611) (FRL-9922-68), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 4E8304) by Sumitomo Chemical Latin America through Valent USA Corporation, 1600 Riviera Avenue, Suite 200, Walnut Creek, CA 94596. The petition requested that 40 CFR 180.593 be amended by establishing tolerances for residues of the insecticide etoxazole (2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5dihydrooxazole), in or on orange and orange oil at 0.08 and 1.8 parts per million (ppm), respectively. That document referenced a summary of the petition prepared by Valent USA Corporation on behalf of Sumitomo Chemical Latin America, the registrant, which is available in the docket, http://www.regulations.gov.
EPA received one comment to the Notice of Filing concerning another chemical (azoxystrobin) and not etoxazole. The commenter stated, in part, that zero residues should be allowed for pesticide residues. The Agency understands the commenter's concerns and recognizes that some individuals believe that pesticides should be banned on agricultural crops. However, the existing legal framework provided by section 408 of the FFDCA states that tolerances may be set when persons seeking such tolerances or exemptions have demonstrated that the pesticide meets the safety standard imposed by that statute. This citizen's comment appears to be directed at the underlying statute and not EPA's implementation of it; the citizen has made no contention that EPA has acted in violation of the statutory framework.
Based upon review of the data supporting the petition, EPA has revised the petitioned-for tolerance levels of 0.08 and 1.8 ppm for orange and orange, oil to 0.10 and 1.0 ppm, respectively. The reasons for these changes are explained in Unit IV.C.
III. Aggregate Risk Assessment and Determination of Safety
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Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a tolerance (the legal limit for a pesticide chemical residue in or on a food) only if EPA determines that the tolerance is safe. Section 408(b)(2)(A)(ii) of FFDCA defines safe to mean that there is a reasonable certainty that no harm will result from aggregate exposure to the pesticide chemical residue, including all anticipated dietary exposures and all other exposures for which there is reliable information. This includes exposure through drinking water and in residential settings, but does not include occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to give special consideration to exposure of infants and children to the pesticide chemical residue in establishing a tolerance and to ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue. . . .
Consistent with FFDCA section 408(b)(2)(D), and the factors specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available scientific data and other relevant information in support of this action. EPA has sufficient data to assess the hazards of and to make a determination on aggregate exposure for etoxazole including exposure resulting from the tolerances established by this action. EPA's assessment of exposures and risks associated with etoxazole follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its validity, completeness, and reliability as well as the relationship of the results of the studies to human risk. EPA has also considered available information concerning the variability of the sensitivities of major identifiable subgroups of consumers, including infants and children.
The effects in the etoxazole database show liver toxicity in all species tested (enzyme release, hepatocellular swelling, and histopathological indicators), and the severity does not appear to increase with time. In rats only, there were effects on incisors (elongation, whitening, and partial loss of upper and/or lower incisors). There is no evidence of neurotoxicity or immunotoxicity. No toxicity was seen at the limit dose in a 28-day dermal toxicity study in rats. Etoxazole was not mutagenic. No increased quantitative or qualitative susceptibilities were observed following in utero exposure torats or rabbits in the developmental studies; however, offspring toxicity was more severe (increased pup mortality) than maternal toxicity (increased liver and adrenal weights) at the same dose (158.7 milligram/kilogram/day (mg/kg/day)) in the rat reproduction study indicating increased qualitative susceptibility. Etoxazole is not likely to be carcinogenic based on the lack of carcinogenicity effects in the database.
Specific information on the studies received and the nature of the adverse effects caused by etoxazole as well as the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in document, Etoxazole: Human Health Risk Assessment in Support of the Proposed Tolerances for Residues in/on Imported Oranges and Orange Oil at pp. 16-18 in docket ID number EPA-HQ-OPP-2014-0681.
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA identifies toxicological points of departure (POD) and levels of concern to use in evaluating the risk posed by human exposure to the pesticide. For hazards that have a threshold below which there is no appreciable risk, the toxicological POD is used as the basis for derivation of reference values for risk assessment. PODs are developed based on a careful analysis of the doses in each toxicological study to determine the dose at which the NOAEL and the LOAEL are identified. Uncertainty/safety factors are used in conjunction with the POD to calculate a safe exposure levelgenerally referred to as a population-adjusted dose (PAD) or a reference dose (RfD)and a safe margin of exposure (MOE). For non-threshold risks, the Agency assumes that any amount of exposure will lead to some degree of risk. Thus, the Agency estimates risk in terms of the probability of an occurrence of the adverse effect expected in a lifetime. For more information on the general principles EPA uses in risk characterization and a complete description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for etoxazole used for human risk assessment is shown in Table 1 of this unit.
Table 1Summary of Toxicological Doses and Endpoints for Etoxazole for Use in Human Health Risk Assessment Back to Top
Exposure/scenarioPoint of departure and uncertainty/safety factorsRfD, PAD, LOC for risk assessmentStudy and toxicological effects
Point of departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). Food Quality Protection Act Safety Factor = FQPA SF. PAD = population-adjusted dose (a = acute, c = chronic). RfD = reference dose. N/A = not applicable.
Acute dietary (all populations)N/AN/AA dose and endpoint attributable to a single dose were not identified in the database including the hazard database. An acute dietary assessment was not performed.
Chronic dietary (all populations)NOAEL = 4.62 mg/kg/day UF A= 10x UF H= 10x FQPA SF = 1xChronic RfD = 0.046 mg/kg/day cPAD = 0.046 mg/kg/dayChronic Oral Toxicity StudyDog. LOAEL = 23.5 mg/kg/day based upon increased alkaline phosphatase activity, increased liver weights, liver enlargement (females), and incidences of centrilobular hepatocellular swelling in the liver.
Cancer (Oral, dermal, inhalation)EPA classified etoxazole as not likely to be carcinogenic to humans.
Since the current proposal pertains to an import tolerance (no occupational exposure for workers in the U.S.) and since residential exposure is not anticipated from the proposed/registered uses, only dietary toxicological endpoints are listed in Table 1.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary exposure to etoxazole, EPA considered exposure under the petitioned-for tolerances as well as all existing etoxazole tolerances in 40 CFR 180.593. EPA assessed dietary exposures from etoxazole in food as follows:
i. Acute exposure. Quantitative acute dietary exposure and risk assessments are performed for a food-use pesticide, if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a 1-day or single exposure.
No such effects were identified in the toxicological studies for etoxazole; therefore, a quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure assessment EPA used the food consumption data from the USDA National Health and Nutrition Examination Survey, What We Eat in America (NHANES/WWEIA; 2003-2008). As to residue levels in food, EPA assumed tolerance-level residues, 100% crop treated (PCT), and in the absence of empirical data, DEEM (ver 7.81) default processing factors. In addition, based on EPA's conclusion that etoxazole has a high potential to bioaccumulate, residue estimates for fish/shellfish were included.
iii. Cancer. EPA classified etoxazole as not likely to be carcinogenic to humans. Therefore, a dietary exposure assessment for the purpose of assessing cancer risk is unnecessary.
iv. Anticipated residue and percent crop treated (PCT) information. EPA did not use anticipated residue and/or PCT information in the dietary assessment for etoxazole. Tolerance-level residues and/or 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. Although the orange and orange, oil tolerances will not result in residues in drinking water, as those uses are notassociated with a U.S. registration, the Agency used screening-level water exposure models in the dietary exposure analysis and risk assessment to assess etoxazole in drinking water resulting from existing U.S. registrations. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of etoxazole. Further information regarding EPA drinking water models used in pesticide exposure assessment can be found at http://www.epa.gov/oppefed1/models/water/index.htm.
Based on the First Index Reservoir Screening Tool (FIRST), and Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS), the estimated drinking water concentrations (EDWCs) of etoxazole for chronic exposures for non-cancer assessments are estimated to be 4.761 parts per billion (ppb) for surface water and <0.1 ppb for ground water.
Modeled estimates of drinking water concentrations were directly entered into the dietary exposure model.
For chronic dietary risk assessment, the water concentration of value 4.761 ppb was used to assess the contribution to drinking water.
3. From non-dietary exposure. The term residential exposure is used in this document to refer to non-occupational, non-dietary exposure (e.g., for lawn and garden pest control, indoor pest control, termiticides, and flea and tick control on pets).
Etoxazole is not registered for any specific use patterns that would result in residential exposure.
4. Cumulative effects from substances with a common mechanism of toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider available information concerning the cumulative effects of a particular pesticide's residues and other substances that have a common mechanism of toxicity.
EPA has not found etoxazole to share a common mechanism of toxicity with any other substances, and etoxazole does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, therefore, EPA has assumed that etoxazole does not have a common mechanism of toxicity with other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA shall apply an additional tenfold (10X) margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database on toxicity and exposure unless EPA determines based on reliable data that a different margin of safety will be safe for infants and children. This additional margin of safety is commonly referred to as the Food Quality Protection Act Safety Factor (FQPA SF). In applying this provision, EPA either retains the default value of 10X, or uses a different additional safety factor when reliable data available to EPA support the choice of a different factor.
2. Prenatal and postnatal sensitivity. No increased quantitative or qualitative susceptibilities were observed following in utero exposure to rats or rabbits in the developmental studies. There is evidence of increased qualitative offspring susceptibility in the rat reproduction study, but the concern is low since: (1) The effects in pups are well-characterized with a clear NOAEL; (2) the selected endpoints are protective of the doses where the offspring toxicity is observed; and (3) offspring effects occur in the presence of parental toxicity. There are no residual uncertainties for pre-/post-natal toxicity.
3. Conclusion. EPA has determined that reliable data show the safety of infants and children would be adequately protected if the FQPA SF were reduced to 1x. That decision is based on the following findings:
i. The toxicity database for etoxazole is complete.
ii. There is no indication that etoxazole is a neurotoxic chemical and there is no need for a developmental neurotoxicity study or additional uncertainty factors (UFs) to account for neurotoxicity.
iii. The observed qualitative postnatal susceptibility is protected for by the selected endpoints.
iv. There are no residual uncertainties identified in the exposure databases.
EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to etoxazole in drinking water. These assessments will not underestimate the exposure and risks posed by etoxazole.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic dietary pesticide exposures are safe by comparing aggregate exposure estimates to the acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA calculates the lifetime probability of acquiring cancer given the estimated aggregate exposure. Short-, intermediate-, and chronic-term risks are evaluated by comparing the estimated aggregate food, water, and residential exposure to the appropriate PODs to ensure that an adequate MOE exists.
1. Acute risk. An acute aggregate risk assessment takes into account acute exposure estimates from dietary consumption of food and drinking water. No adverse effect resulting from a single oral exposure was identified and no acute dietary endpoint was selected. Therefore, etoxazole is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this unit for chronic exposure, EPA has concluded that chronic exposure to etoxazole from food and water will utilize 15% of the cPAD for children 1-2 years old the population group receiving the greatest exposure. There are no residential uses for etoxazole.
3. Aggregate cancer risk for U.S. population. Based on the lack of evidence of carcinogenicity in two adequate rodent carcinogenicity studies, etoxazole is not expected to pose a cancer risk to humans.
4. Determination of safety. Based on these risk assessments, EPA concludes that there is a reasonable certainty that no harm will result to the general population, or to infants and children from aggregate exposure to etoxazole residues.
IV. Other Considerations
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A. Analytical Enforcement Methodology
Adequate enforcement methodology gas chromatography/nitrogen phosphorus detector (GC/NPD) is available to enforce the recommended tolerances.
The method may be requested from: Chief, Analytical Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; email address: residuemethods@epa.gov.
B. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S. tolerances with international standards whenever possible, consistent with U.S. food safety standards and agricultural practices. EPA considers the international maximum residue limits (MRLs) established by the Codex Alimentarius Commission (Codex), asrequired by FFDCA section 408(b)(4). The Codex Alimentarius is a joint United Nations Food and Agriculture Organization/World Health Organization food standards program, and it is recognized as an international food safety standards-setting organization in trade agreements to which the United States is a party. EPA may establish a tolerance that is different from a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain the reasons for departing from the Codex level.
The Codex has established MRLs for etoxazole in or on citrus fruits at 0.1 ppm. EPA is establishing a tolerance for residues in or on orange of 0.10 ppm in order to harmonize with the Codex MRL.
C. Revisions to Petitioned-For Tolerances
EPA has revised the proposed tolerance levels for orange and orange oil from 0.08 and 1.8 ppm to 0.10 and 1.0 ppm, respectively. EPA is establishing a tolerance of 0.10 ppm for orange in order to harmonize with the Codex MRL. Additionally, based on the orange raw agricultural commodity highest-average field-trial residue of 0.048 ppm and the median orange oil processing factor of 20x, EPA is establishing a tolerance for orange, oil at 1.0 ppm. In addition, EPA is revising the commodity terms for orange oil to read as orange, oil to be consistent with the Agency's commodity vocabulary.Show citation box
V. Conclusion
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Therefore, tolerances are established for residues of etoxazole (2-(2,6-difluorophenyl)-4-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydrooxazole), in or on orange and orange, oil at 0.10 ppm and 1.0 ppm, respectively.
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